AIDS and HIV infection have reached epidemic proportions and a vaccine, as well as effective treatment, is urgently needed. Better understanding of HIV neutralizing antibodies is critical to the vaccine effort. Previous studies by several investigators, including the PI, have shown that HIV neutralizing antibodies (1) can be detected in serum of most infected individuals, (2) are primarily directed against envelope glycoproteins, gp 120 and gp 41, and (3) from human sera can neutralize diverse heterologous HIV isolates, although antibodies elicited in animals generally show type- specific neutralization. In addition, utilizing antisera raised against synthetic oligopeptides, the PI has identified four domains in gp d120 and gp 41 which are targets for neutralization. Furthermore, preliminary findings suggest that there may be envelope domains which can elicit antibodies capable of either enhancing HIV infection in vitro or blocking the action of neutralizing antibodies. The proposed investigations will employ two major approaches to define the domains important in HIV neutralization. The first will utilize recombinant and synthetic peptides to isolate specific immunoglobulin fractions from human neutralizing sera by affinity chromatography. The second will involve immunization of laboratory animals with recombinant and synthetic peptides to raise specific antisera. In a neutralization assay, the activity of these mono-specific human and animal antibody preparations to neutralize HIV will be determined using multiple diverse isolates. Subsequently, studies will be initiated to explore the mechanism of action of neutralizing antibodies. In addition, the non- neutralizing antibodies will be examined for possible enhancement of HIV infection and for blocking effect on neutralizing antibodies. The results of these studies may form the basis for the rational design of a vaccine for AIDS.